Jane A. Smith, Ph.D., is a lecturer in the
Department of Biomedical Science and Biomedical
Ethics at the University of Birmingham Medical School in Birmingham, England.

INTRODUCTION

Quite apart from philosophical considerations,
practical and scientific evidence may lead us to
assume that all mammals can experience something
analogous to (though most likely qualitatively
and quantitatively different from) the human
experience of pain. Humans, after' all, are
mammals; and although the details may differ, we
share our basic physiology with other mammalian
species. There is also a reasonableness, it
seems, in extending this view to include other
members of the Vertebrata. The further we move
away from the mammalian plan, the more difficult
it becomes to infer pain in other species. But
vertebrates, at least, have similarities in basic
anatomy and physiology, including similarities in
nervous organization, which are especially important in this context.

What, however, of the 95 percent of species in
the Animal Kingdom that do not possess a
backbone--the heterogeneous assemblage of
animals, organized very differently from the
vertebrate plan, which we call "invertebrates"?

Invertebrates are used in many disciplines in
biomedical research and also in toxicity testing.
Sometimes, invertebrate species are regarded as
"replacement" alternatives for vertebrates
(Office of Technology Assessment, 1986),
presumably because they are thought to be
insentient, or at least less sentient than vertebrate animals.

Is this contention true? Can any of the
invertebrates experience pain in anything like
the human, or the more general vertebrate, sense?
Can these animals, in this sense, "suffer"?

This short paper approaches such questions i:rom
a practical, rather than a philosophical, point
of view. Some biological evidence relating to the
possibility of pain in invertebrates is reviewed,
and some practical implications are raised.

There are unlikely to be any easy answers to the
difficult question of assessing pain in
invertebrates. It is hoped, however, that the
following discussion will provide some food for
thought and help to stimulate further debate.

EVIDENCE OF NOCICEPTION IN INVERTEBRATES

Most, if not all, invertebrates have the capacity
to detect and respond to noxious or aversive
stimuli. That is, like vertebrates, they are
capable of "nociception." Examples of aversive
stimuli include changes in temperature beyond the
animal's normal range, contact with noxious
chemicals, mechanical interference, or electric
shock. Under certain conditions, all of these
might be expected to cause pain in humans. In
general, invertebrates, like vertebrates, respond
to such stimuli by withdrawing or escaping so as
to reduce the likelihood that they will be damaged by the noxious conditions.

Behavioral Responses of Invertebrates to Noxious Stimuli

Even the "simplest" invertebrates, the
single-celled Protozoa, exhibit nociceptive-type
responses. The ciliated protozoon Paramecium, for
example, changes the rate and form of its ciliary
beat in response to aversive stimulation (such as
a poke with a fine needle) so as to effect
typical avoidance and escape reactions. The
animals, of course, have no nervous systems to
coordinate such responses; rather, these changes
in behavior are triggered by changes in the
electrical activity of the cell surface membrane (Naitoh, 1974).

As a detailed review by Kavaliers (1988)
describes, all other invertebrates (with the
possible exception of the Porifera, or sponges),
can also exhibit coordinated responses to
aversive stimuli. Thus, to take a few examples:
* sea anemones show protective withdrawal
responses by retracting their tentacles and oral
disc. Some may even detach from the substrate in
response to a variety of i aversive mechanical,
electrical, or chemical stimuli (Pantin, 1935; Ross, 1968);
* earthworms show rapid withdrawal reflexes
mediated by giant nerve fibers when subjected to unfavorable stimuli;
* medicinal leeches show pronounced writhing
and coiling responses when their skin is pinched
or damaged (Nicholls and Baylor, 1968);
* insects have a variety of avoidance and
escape responses (Eisemann et al., 1984), and
appear also to exhibit physiological changes to
aversive stimuli (Angioy et al., 1987). They may
be more responsive to some stimuli than to
others. Thus, most insects "do not flinch or
run," when the cuticle is cut, but high
temperature (such as a heated needle brought
close to the antennae) can produce violent escape
responses (Wigglesworth, 1980);
* gastropod snails of the species Cepaea
nemoralis show foot-lifting responses when placed
on a surface wanned to temperatures approaching
40� C, which is above their normal range (Kavaliers and Hirst, 1983); and
* cephalopod mollusks, such as octopuses, may
respond to noxious stimuli by withdrawing,
sometimes producing a cloud of ink from the ink
sac, and usually changing color.

Invertebrate Nociceptors

Some invertebrates, like vertebrates, also have
special sensory receptors called nociceptors,
which respond specifically to noxious
stimulation. Such nociceptive nerve cells have
been found in the segmental ganglia of the
medicinal leech, Hirudo medicinalis (Nicholls and
Baylot, 1968). Nerve impulses are generated in
these cells, which Nicholls and Baylor called N
cells, specifically in response to noxious
mechanical stimulation, such as pinching,
squeezing, or cutting of the body wall.

Modulation of Nociceptive Responses in Invertebrates

In mammals and other vertebrates, opioid
substances (including enkephalins and endorphins)
manufactured in the body can modify nervous
transmission in nociception, producing analgesic
effects. Administration of substances that mimic
the effects of these endogenous opioids (i.e.,
administration of opiate agonists, such as
morphine), also produces analgesia and thus may
reduce or abolish behavioral responses to noxious
stimuli. Furthermore, opiate antagonists such as
naloxone may suppress these analgesic effects.
Recent investigations have shown that similar
opiate systems may have a functional role in
invertebrate nociception (Fiorito, 1986; Kavaliers, 1988).

Enkephalin and b-endorphin-like substances have
been found in earthworms (Alumets et al., 1979),
and injections of nalaxone have been shown to
inhibit the worms' touch-induced escape responses
(Gesser and Larsson, 1986), suggesting that the
opioid substances may play a role in sensory
modulation. Opiate binding sites, with properties
similar to those of mammalian opiate receptors,
have been shown to be present in the neural
tissue of the marine mollusk Mytilus edulis
(Kavaliers et al., 1985). Kavaliers et al. (1983,
1985) have shown that administration of low doses
of the opioid peptides methionine-enkephalin and
b-endorphin produces "analgesic" effects in
terrestrial snails of the species Cepaea
nemoralis and that morphine has a similar effect.
All three substances increase the time taken for
the snails to respond by foot-lifting when placed
on a 40� C hot plate. Furthermore, naloxone has
been found to abolish the effect of morphine, and
all of the effects were dose-dependent.

Enkephalin-like substances and their receptors
have also been found in insects (Stefano and
Scharrer, 1981; EI-Salhy et al., 1983), and
opiate agonists and antagonists have been shown
to modulate nociceptive-type responses in several
species of arthropod, including mantis shrimps
(Squilla mantis) (Maldonado and Miralto, 1982),
honeybees (Nfinez et al., 1983), and praying mantes (Zabala et al., 1984.

EVIDENCE OF PAIN IN INVERTEBRATES

Invertebrates, it seems, exhibit nociceptive
responses analogous to those shown by
vertebrates. They can detect and respond to
noxious stimuli, and in some cases, these
responses can be modified by opioid substances.
However, in humans, at least, there is a
distinction to be made between the "registering"
of a noxious stimulus and the "experience" of
pain. In humans, pain "may be seen as the
response of the whole awake conscious organism to
noxious stimuli, seated.., at the highest levels
in the central nervous system, involving
emotional and other psychological components"
(Iggo, 1984). Experiments on decorticate mammals
have shown that complex, though stereotyped,
motor responses to noxious stimuli may occur in
the absence of consciousness and, therefore, of
pain (Iggo, 1984). Thus, it is possible that
invertebrates' responses to noxious stimuli (and
modifications of these responses) could be simple
reflexes, occurring without the animals being
aware of experiencing something unpleasant, that
is, without "suffering" something akin to what humans call pain.

Leaving aside the conceptual questions which
arise in trying to understand what other
individuals (of our own or other species) might
experience, it might be asked whether there is
any practical, physiological, or behavioral
evidence that could lead us to infer that
particular invertebrates might or might not
experience pain. What evidence might help in
distinguishing between nociceptive "responsiveness" and the perception of pain?

At the outset, it should be pointed out that
because pain is a subjective experience, it is
highly unlikely that any clear-cut, definitive
criteria will ever be found to decide this
question. However, certain evidence might lead to
judgements that pain is more or less likely to
occur in one particular kind of invertebrate than
in another kind. In particular, it can be argued
that evidence might come from further examination
of an animal's behavioral responses to noxious
stimulation and from consideration of the
complexity of its nervous organization (Smith and Boyd, 1991).

In mammals, responses to painful stimuli often
persist beyond a simple reflex withdrawal, so
that, for example, the animals may become
immobile, limp or "guard" the affected part, show
aggression when approached, reduce or stop
feeding and drinking, and show decreased sexual
activity (Morton and Griffiths, 1985). The
animals may also learn in the future to avoid
situations similar to the one in which the pain
occurred. Such responses, while not proof that
the animals have experienced pain, can indicate
that something more than a simple nociceptive
reflex is involved. Together, they may help the
animal to recover from damage caused by the
painful event and avoid being harmed in the future.

Insects and "Less Complex" Invertebrates

In the majority of examples of invertebrate
nociception noted above, there seems to be
little, if any, evidence that the animals'
responses persist in anything akin to the manner
described for mammals. As Eisemann et al. (1984)
have described in a review of the "biological
evidence" concerning pain in insects, "No example
is known to us of an insect showing protective
behavior towards injured parts, such as by
limping after leg injury or declining to feed or
mate because of general abdominal injuries. On
the contrary, our experience has been that
insects will continue with normal activities even
after severe injury or removal of body parts."

Eisemann et al. (1984) use a variety of examples
to support this contention, including:
* an insect walking with a crushed tarsus
continues "applying it to the substrate with undiminished force";
* a locust carries on feeding while being eaten by a mantis;
* a tsetse fly, although half-dissected, flies in to feed.
Although some insect behavior, such as the
writhing of insects poisoned by insecticides, or
the struggling of restrained living insects,
resembles that of "higher animals responding to
painful stimuli," Eisemann et al. conclude that
the resemblance is superficial and that it "no
more requires the presence of a pain sense than
do reflexive withdrawal responses." Similarly,
although it has been shown that fruit flies can
be trained to avoid certain odors and colored
lights when these are associated with impending
electric shock (Quinn et al., 1974), such
learning is open to explanation in terms of
neural mechanisms, without the need to postulate
subjective experience on the part of flies.

The "relatively simple organization" of the
insect central nervous system, Elsemann et al.
argue, "raises the question of whether any
experience akin to human pain could be generated"
in these animals (and by implication in other
invertebrates with a similar or less complex
nervous organization). On the analysis of Gould
and Gould (1982), the answer to such a question
would be "no," for these authors can find no
evidence for conscious experience in insects.
Certainly, on the limited amount of evidence
presented here, it seems very difficult to
imagine that insects and the other simpler
invertebrates mentioned above can "suffer" pain
in anything like the vertebrate sense.
Nevertheless, the issue certainly is not closed,
and further questions should be asked.

Perhaps such a view simply reflects a paucity of
(human) imagination. Griffin (1984) surely would
urge us to maintain an open mind on the issue,
having provided behavioral evidence which, he
argues, should challenge "the widespread belief'
that an insect, for example, "is too small and
its central nervous system too differently
organized from ours to be capable of conscious
thinking and planning or subjective feelings."
Indeed, to take a more radical view, perhaps "it
is presumptuous for us to assume that because our
suffering involves self-awareness, this should
also be true of other species" (McFarland, 1989).

Alternatively, perhaps, as Mather (1989)
suggests, we should simply accept that these
animals "are different from us, and wait for more data."

Cephalopods

Perhaps the question of pain in invertebrates
could be more easily settled where the "most
highly organized of all invertebrates"
(Russell-Hunter, 1979), the cephalopods, are concerned.

These animals, which include cuttlefish, squid,
and octopuses, "have the largest brains of all
invertebrates" (Wells, 1962). The ratio of
brain-weight to body-weight of many cephalopods
also exceeds that of most fish and reptiles
(Packard, 1972). The cephalopod brain has a
"hierarchical" organization (see Boycott, 1961),
the "higher" centers of the brain being concerned
with sensory analysis, memory, learning, and
decision-making. It has been suggested that these
areas of the cephalopod brain might be regarded
as analogous to the cerebral cortex of higher
vertebrates (Russell-Hunter, 1979). According to
Wells (1978), since in Octopus the brain
"represents only the more specialized sensory
integrative, higher movement control and learning
parts of a rather diffuse nervous system...it
becomes clear that one is dealing with an animal
that might well be expected to possess a central
nervous capability approaching that or exceeding
that of many birds and mammals."

Cephalopods show a remarkable ability to learn
and to be trained. In learning experiments,
Octopus vulgaris "clearly generalizes on the
basis of its own past experience,'' and the
animals may show marked individual preferences
(Wells, 1978). Anecdotal reports suggest
considerable individuality of behavior. Dews
(1959) describes how one of the octopuses he was
using in training experiments "spent much time
with eyes above the surface of the water,
directing a jet of water at any individual who approached the tank."

The evidence seems to suggest that at least some
of the cephalopods might have a nervous
organization that would allow them to experience
something like pain. It is unclear, however,
whether cephalopods are able to "suffer" pain.

Certainly, noxious stimuli such as electric
shocks are effective "negative reinforcers" when
used for training cephalopods in discrimination
learning experiments. It seems also that repeated
noxious stimulation can have long-term effects on
behavior. Wells (1978) describes the adverse
effects of repeated electric shocks given to
blinded octopuses. He describes how blinded
octopuses will normally be found sitting in their
tanks with their arms outstretched, allowing for
a "very standardized presentation'' of test
objects in tactile discrimination experiments.
However cases in which "the animal has become
withdrawn as a result of making large numbers of
errors and receiving many shocks in the course of
training, it is not so easy. Considerable
practice may then be required to recognize which
arm is in which tangle, and some delicacy may be
needed in presenting test objects since the
suckers are very sensitive and the animal may shy away from contacts."

Both Young's (1965) and Wells' (1978) models of
learning in the octopus include a "pain" pathway
leading into the "highest" center (the vertical
lobe) of the brain. Wells, however, notes that
although this nervous path is "generally assumed
to signal 'pain'...there is no proof of this and
it might well carry 'pleasure' or any other 'signal' ".

Although the evidence for pain perception is
equivocal, it seems that cephalopods might
exhibit body postures, color patterns and
behaviors that the human observer can interpret
as signaling, at least, whether or not "something
is wrong" with those animals. An anecdotal
example is quoted by Lane (1974), from Joseph
Sinel (1906), who handled hundreds of common
octopuses. "When highly content, as after a meal,
and perched, as it is fond of perching at times,
upon an eminence, the papillae [pimple-like
projections on the skin] are erected and these
are always of an orange color. Oftentimes the
whole body will be marked off in irregular,
honeycomb-like patches, or more like
crocodile-skin. First some of the patches are
purple, others orange, then these colors are
reversed. When danger threatens, or even when the
hand is raised towards it as if to strike, the
animal winces, and turns to ashy grey."

Mather (1989) describes how "...when I recently
had two octopuses in one aquarium and one of the
animals changed from its known daytime activity
in a hidden location and took on a coloration
previously associated with aversire stimuli, I
surmised before I saw the other animal attack it that there was a problem."

Wells (1978), however, is more guarded about
human abilities to empathize with these animals.
He agrees that it is very easy for humans "to
identify with Octopus vulgaris, even with
individuals, because they respond in a very
'human' way." Nevertheless, he argues, the
octopus has a very different way of life, and
"...we should not fall into the trap of supposing
that we can interpret its behavior in terms of
concepts derived from birds or mammals [since]
the animal lives in a very different world from our own."

It is important to bear in mind this caveat when
considering evidence concerning pain in
cephalopods. Nevertheless, the evidence certainly
does not preclude the possibility of pain in
these animals and, moreover, suggests that pain
is more likely in cephalopods than in the other
invertebrates with less "complex" nervous
organizations, considered in this review.

Comparisons between cephalopods and fish could
lend weight to this conclusion. Packard (1972)
has provided a comprehensive review of the
similarities between cephalopods and fish. He
concludes that "it might reasonably be argued
that the similarities between fish and
cephalopods are greater than between any other
two major groups belonging to different phyla.
The remarkable fact that cephalopods are like
fish in almost every other feature except in
their basic anatomical plan--that is, in its
simplest expression, cephalopods functionally are
fish--seems to have passed largely unnoticed."
Thus, if it can be agreed that fish have the
ability to perceive pain, this would suggest that
the possibility that cephalopods also feel pain
should be taken all the more seriously.

CONCLUSION: SOME PRACTICAL "WAYS FORWARD"

Clearly, in all this, there is the danger of
adopting an uncritical anthropomorphic (or, in
this context, perhaps a "vertebromorphic")
approach, which could lead to incorrect
conclusions about the experiences of invertebrates
(see Morton et al., 1990). Thus, it might be
inferred, incorrectly, that certain invertebrates
experience pain simply because they bear a
(superficial) resemblance to vertebrates-the
animals with which humans can identify with most
clearly. Equally, pain might incorrectly be
denied in certain invertebrates simply because
they are so different from us and because we
cannot imagine pain experienced in anything other
than the vertebrate or, specifically, human sense.

This limitation should be borne in mind when
considering the practical implications of the
tentative conclusions drawn from the evidence
presented above. Although pain might seem less
likely in the more "simple" invertebrates, than
in the most "complex" invertebrates, such as the
cephalopod mollusks (and, perhaps, decapod
crustaceans such as crabs and lobsters, not
considered here), this certainly does not mean
that the more "simple" invertebrates ought not to be afforded respect.

A principle of respect should lead those who use
invertebrates in research (or display them in
zoos, rear them for food, and so on) to try to
maintain the highest possible standards of
husbandry and care, so as to promote the animals'
general "well-being" and, whenever practicable,
to give the animals the benefit of the doubt
where questions of pain and suffering are concerned.

The well-being of invertebrates used for research
is being taken increasingly seriously.
Wigglesworth (1980), for example, has suggested
that for practical purposes it should be assumed
that insects feel pain and that they should,
therefore, be narcotized in procedures that have
the potential to cause pain. Cooper (1990) has
identified several practical ways in which the
well-being of invertebrates might be promoted. These include:
* providing husbandry conditions that match,
as closely as possible, those preferred by the species in the wild;
* assuring high standards of care, provided
by staff with an interest in invertebrates;
* avoiding unnecessary or insensitive handling or restraint;
* narcotizing the animals for any invasive or
disruptive procedures and during prolonged
restraint (some methods of anesthesia are described by Cooper, 1990) and;
* where possible, avoiding the use of the more "complex'' species.

To this list might be added:
* attempting to kill invertebrates by the
most humane methods possible and;
* providing suitable guidance and training
for all involved in the care and use of these animals.

Recently, the Canadian Council on Animal Care
(CCAC) established a Committee on Invertebrates
(CCAC, 1988a), and in the U.K., the Universities
Federation for Animal Welfare (UFAW) has
published a handbook on the care of cephalopods
in the laboratory (Boyle, 1991). Guidance on
caring for invertebrates might also come from
groups that keep these animals for purposes other
than research. In 1987, the National Federation
of Zoological Gardens of Great Britain and
Ireland convened a Working Group on
Invertebrates. Among other activities, this group
is producing codes of practice for those who keep
invertebrates. The second of these codes gives
guidance on methods of humane killing (National Federation of Zoos, 1990).

Consideration is also being given to including
invertebrates, especially the cephalopods, under
some systems of control of animal experiments.
Most such statutory or non-statutory systems
cover only vertebrate species. However, the
CCAC's list of "Categories of Invasiveness in
Animal Experiments" recognizes that "cephalopods
and some other higher invertebrates have nervous
systems as well developed as some vertebrates"
and so might be included in categories in which
pain and distress (including "severe pain") is
caused. Protocols involying these "higher"
invertebrates must be evaluated and approved by
an Animal Care Committee before the work can
commence (CCAC, 1988b). It has been suggested in
the U.K. also that there might be a case for
including cephalopods under the terms of the
Animals (Scientific Procedures) Act 1986 (Report
of a Working Party of the Institute of Medical
Ethics) (Smith and Boyd, 1991). Currently, the
Act protects only vertebrate animals, but its
terms provide for protection to be extended to
cover "invertebrates of any description" if, in
the future, this is thought appropriate. Whether
the inclusion of invertebrates species under
laboratory animal protection laws is indeed the
way forward is open to further discussion. Such a
debate, nevertheless, helps to promote careful
consideration of the use of all animals in
research, not simply the use of animals which possess backbones.

The question of pain in invertebrates will be
extremely difficult to resolve--if, indeed, it is
resolvable. In the meantime, perhaps it can be
agreed that it is most appropriate to concentrate
efforts on maintaining and improving the general
well-being of invertebrates used in research,
that is, to ensure that these animals are kept in
the best and most appropriate conditions during
their lives in the laboratory; given the benefit
of the doubt in procedures which have the
potential to cause pain and distress; and, when
the time comes, killed in the most humane manner possible.

ACKNOWLEDGEMENT

I am very grateful to the Institute of Medical
Ethics and the Leverhulme Trust for their support
in the preparation of this paper, which was
written while working for the Institute of
Medical Ethics' Working Party on the Ethics of
Using Animals in Biomedical Research.

National Federation of Zoos. 1990. Euthanasia of
Invertebrates. Codes of Practice for the Care of
Invertebrates in Captivity, 2. London: National
Federation of Zoological Gardens of Great Britain and Ireland.

Russell-Hunter, W. D. 1979. A Life of Invertebrates. New York:Macmillan.

Sinel, J. 1906. An Outline of the Natural History
of Our Shores. London: Sonnenschein.

Smith, J. A., and K. M. Boyd. eds. 1991. Lives in
the Balance: The Ethics of Using Animals in
Biomedical Research (Report of a Working Party of
the Institute of Medical Ethics). Oxford: Oxford University Press.